title: Rabaptin-5 and Rabex-5 are neoplastic tumour suppressor genes that interact to modulate Rab5 dynamics in Drosophila melanogaster.
abstract: Endocytosis plays an important role in the regulation of tumour growth and metastasis. In Drosophila, a number of endocytic neoplastic tumour suppressor genes have been identified that when mutated cause epithelial disruption and over-proliferation. Here we characterise the Drosophila homologue of the Rab5 effector Rabaptin-5, and show that it is a novel neoplastic tumour suppressor. Its ability to bind Rab5 and modulate early endosomal dynamics is conserved in Drosophila, as is its interaction with the Rab5 GEF Rabex5, for which we also demonstrate neoplastic tumour suppressor characteristics. Surprisingly, we do not observe disruption of apico-basal polarity in Rabaptin-5 and Rabex-5 mutant tissues; instead the tumour phenotype is associated with upregulation of Jun N-terminal Kinase (JNK) and Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signalling.
authors.affiliation: MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Thomas
authors.forename: David
authors.initials: D
authors.lastname: Strutt
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D016147:Genes, Tumor Suppressor; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D053612:Janus Kinases / Q000096:biosynthesis / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D050791:STAT Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C586290:Rbpn-5 protein, Drosophila; D050791:STAT Transcription Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D053612:Janus Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C586289:Rab5 protein, Drosophila; D020696:rab5 GTP-Binding Proteins; C553811:Rabex-5 protein, Drosophila
keywords: Drosophila; Endocytosis; Neoplastic tumour suppressor; Rab5; Rabaptin5; Rabex5